How Does Coronavirus Kill? Clinicians Trace a Ferocious Rampage Through the Body

Seizures, kidney failure and respiratory problems are just a few of the symptoms witnessed by physician Joshua Denson during his recent rounds at an intensive care unit. A few days later, he watched as a young woman failed to be resuscitated by his team. Denton, a critical care and pulmonary physician from the Tulane University School of Medicine, shares that these cases all share one striking similarity: “They are all COVID positive.”

Across the globe, the number of confirmed COVID-19 cases has surpassed 2.2 million, with the death toll over 150,000. Pathologists and medical professionals are having trouble comprehending the damage inflicted throughout the body by the coronavirus. What they do know is that the damage from the virus originates in the lungs and can reach other vital organs such as the kidneys, blood vessels, brain, gut and heart.

Harlan Krumholz, a cardiologist at Yale-New Haven Hospital and Yale University, warns that the disease “can attack almost anything in the body with devastating consequences. Its ferocity is breathtaking and humbling.”

Doctors desperately need additional research and knowledge to better treat infected patients as they take a quick turn for the worse. Is blood clotting the reason some healthy patients become seriously ill? Can drugs that are immune-suppressing help in cases where the immune system is overworking? Why are patients not gasping for air when their blood oxygen levels are extremely low? Nilam Mangalmurti, a pulmonary intensivist at the Hospital University of Pennsylvania, says, “Taking a systems approach may be beneficial as we start thinking about therapies.”

Information on how the coronavirus attacks the body’s cells is rapidly evolving, but is truly only scratching the surface in explaining how about 5% of patients are in critical condition. While the virus is often compared to the flu, research is showing that COVID-19 is unlike any virus we’ve seen. Since large-scale studies are just now beginning, scientists are forced to rely on the information from smaller studies that have not been substantiated or reviewed by peers. “We need to keep a very open mind as this phenomenon goes forward,” says physician Nancy Reau, who has been treating patients at Rush University Medical Center. “We are still learning.”

7. How the Infection Begins

COVID-19 (or SARS-CoV-2) is typically transferred from one person to another through the nose and throat. This occurs when an infected person projects droplets that contain the virus and another person breathes in these droplets. According to a report from Wellcome Sanger Institute and other institutions, the virus then adheres to the nose lining. The virus is attracted to tissues with cells that include the angiotensin-converting enzyme 2 (ACE2). The purpose of ACE2 in the body is for blood pressure regulation, and it also acts as a receptor for the virus to access the cell. The virus then takes over the cell, copies itself and infects other cells.

During the first week, infected people begin to release the virus as it multiplies. People may be asymptomatic or they may experience some or all of the six common symptoms, including cough, fever, shortness of breath, headaches, body aches and loss of smell or taste.

At this point, the immune system may win the fight against COVID-19. If not, the virus then heads to the lungs and a fatal attack can begin. The alveoli, small air sacs in the respiratory system of the lungs, contain the vulnerable ACE2 cells. As the cells become infected, this interrupts the transfer of oxygen from the sacs to the capillaries and then the entire body. Chemokines are then released by white blood cells to help with the inflammation. This reaction triggers healthy cells to destroy the virus. The result is pus from the dead cells and an abundance of fluid in the lungs. Patients can recover with assistance from nasal oxygen tubes, while others are not as lucky.

The worst-case scenario is that some patients will develop acute respiratory distress syndrome (ARDS). Breathing becomes incredibly difficult as oxygen levels drop dangerously low. Lungs that have been x-rayed will show cloudy lungs instead of blank space for air. Ventilators are used to help with breathing. A large percentage of patients die as the sacs in the lungs overflow with white blood cells, pus, mucus and fluid.

6. Other Organs at Risk

While we know the potential damage COVID-19 can inflict on the lungs, the virus and the response from the body are clearly hurting other organs as well. Scientists do not know the extent of the damage at this time.

Brain: Infected patients can experience seizures, confusion, strokes, and inflammation of the brain. It is unknown if these symptoms are directly related to the coronavirus.

Eyes: Very ill patients commonly have inflammation of the eye and infections such as conjunctivitis.

Nose: Scientists believe the reason why some patients lose their sense of smell is because the virus damages cells as it passes through the nerve endings.

Heart and blood vessels: Coronavirus patients are experiencing heart attacks, inflammation and blood clots. The virus is attacking cells along the blood vessels through the ACE2 receptors.

Liver: Enzyme levels have shown to be high in a large number of hospitalized patients. This indicates that the liver is being damaged as the immune system is overworked, as well as potential side effects from the drugs being used to treat the virus.

Kidneys: In serious cases, kidney damage is common and deadly. Either the virus directly attacks the kidneys or it is a result of issues such as low blood pressure that affect the entire body.

Intestines: Cells in the lower gastrointestinal tract are attacked by the virus, as they are high in ACE2 receptors. Diarrhea is present in a small percentage of patients (20%).

5. Cytokine Storm

Clinicians think the “cytokine storm” may be the reason why some sick patients’ health is deteriorating so quickly. A cytokine storm is when the level of cytokines needed to signal a healthy immune response is beyond what is needed to fight the virus. As a result, the immune cells fight against the virus, but also against healthy tissues by mistake. This can cause drops in blood pressure, blood clots, leaky blood vessels and organ failure.

High levels of cytokines have been present in the blood of infected patients in some studies. “The real morbidity and mortality of this disease is probably driven by this out of proportion inflammatory response to the virus,” says pulmonologist Jamie Garfield, from his experience at Temple University Hospital treating COVID-19 patients.

However, others disagree. Pulmonary critical care physician Joseph Levitt at the Stanford University School of Medicine argues, “There seems to have been a quick move to associate COVID-19 with these hyperinflammatory states. I haven’t really seen convincing data that that is the case.” Levitt is concerned that reducing the cytokine response could cause other damage. Current clinical trials are testing certain cytokines in infected patients. Levitt worries these drugs may inhibit the immune system from fighting the virus. He says, “There’s a real risk that we allow more viral replication.”

4. Reviewing the Heart

Other scientists are studying the virus’s impact on the heart and blood vessels and arguing this is the real reason the virus can become deadly.

In Italy, a woman in her 50s entered the emergency room with all the signs of a heart attack. Tests of her heart and blood indicated her heart muscles were showing scarring and swelling. In addition, more testing showed an incredibly weak left ventricle only pumping a third of the typical amount of blood. However, when dye was injected into her coronary arteries, they showed no blockages to prove a heart attack. How was this possible? Another test came back positive, this one for COVID-19.

At this time, it is unknown how the virus damages blood vessels and the heart, but studies are showing this is common. JAMA Cardiology confirmed that around 80 of 416 coronavirus patients studied in Wuhan, China had heart damage. Heart arrhythmias were also present in 44% of patients from another Wuhan study.

The blood itself is also being affected. According to a paper in Thrombosis Research, in a Dutch ICU, 38% of the 184 COVID-19 patients experienced abnormal blood clots and a third of them have preexisting clots. In COVID-19 patients, pulmonary embolism has proven deadly when blood clots break up and end up blocking critical arteries in the lungs. Stroke can also occur if these arteries clots transfer to the brain. Behnood Bikdeli, who specializes in cardiovascular medicine at Columbia University Medical Center, has seen many infected patients with a high number of blood clot byproducts such as D-dimer. Bikdeli says, “The more we look, the more likely it becomes that blood clots are a major player in the disease severity and mortality from COVID-19.”

Constriction in the blood vessels has also been occurring in infected patients. Some experience reduced blood flow in the fingers and toes, causing pain, swelling, and tissue damage.

Blood clots play an important role in the COVID-19 infection, making it deadly to some patients. In trying to understand how COVID-19 has caused pneumonia in some patients, blood vessel constriction in the lungs may be the answer. This also explains why some patients’ blood oxygen levels are very low, but they aren’t gasping for air. One theory is that the virus may be offsetting the hormones responsible for blood pressure regulation and allowing the blood vessels to the lungs to become constricted. The constriction instead of the clogged sacs in the lungs causes the lack of oxygen. Levitt says, “One theory is that the virus affects the vascular biology and that’s why we see these really low oxygen levels.”

This theory explains why patients with high blood pressure and diabetes are at higher risk since their blood vessels are already damaged. The CDC produced data that in 14 states, over half of hospitalized patients had high blood pressure, and a third had lung disease or diabetes.

“It’s very striking to us that risk factors seem to be vascular: diabetes, obesity, age, hypertension,” says Mangalmurti. She expected there to be more patients with preexisting respiratory diseases such as asthma.

The damage to the heart and blood vessels is still perplexing to scientists. This could be because they both contain large amounts of ACE2 receptors. Another thought is that the damage is from the lack of oxygen and the overall state of the lungs during the infection, while an additional theory is that the cytokine storm might be inflicting damage to the heart in the same way as the lungs.

Krumholz says, “We’re still at the beginning. We really don’t understand who is vulnerable, why some people are affected so severely, why it comes on so rapidly … and why it is so hard [for some] to recover.”

3. Kidney Damage

The world has been worried about potential shortages of ventilators due to the prevalence of lung failure. However, we should be worried about the lack of enough machines for dialysis. The kidneys are rich in ACE2 receptors, making them a target for the virus. Neurologist Jennifer Frontera has reported from her experience treating coronavirus patients that “if these folks are not dying of lung failure, they’re dying of renal failure.” In order to support all the patients, her hospital is developing different machines for dialysis.

“The lung is the primary battle zone. But a fraction of the virus possibly attacks the kidney. And as on the real battlefield, if two places are being attacked at the same time, each place gets worse,” says neuroscientist Hongbo Jia.

2. How the Brain Is Being Affected

The brain and central nervous system are also showing unique symptoms in response to COVID-19. Frontera and other medical professionals have witnessed strokes, seizures, loss of consciousness, loss of the sense of smell, encephalitis (brain inflammation) and “sympathetic storms” in COVID-19 patients. These “sympathetic storms” are when the sympathetic nervous system goes into overdrive, similar to what happens after serious brain injury. Clinicians wonder if the infection is blocking the brain from recognizing the lack of oxygen in the blood. This could explain why patients aren’t struggling to breathe despite their blood oxygen levels being so low.

Physician Robert Stevens from Johns Hopkins Medicine has confirmed that the brain stem and neural cortex contain ACE2 receptors, but it’s unknown if the virus is able to enter these receptors through the brain. The damage in the brain could be from the cytokine storm or the blood clots and not the virus directly. However, the SARS virus was able to penetrate neurons, and a recent case study in Japan found that the coronavirus had infiltrated the central nervous system through cerebrospinal fluid.

At the University of Pittsburgh Medical Center, Sherry Chou has started a research group with 50 other centers to try to gather neurological data to further understand how the virus affects the brain and the nervous system.

1. Reaching the Gut

The American Journal of Gastroenterology (AJG) reported that a woman from Michigan contracted the virus after returning home sick from Africa. Her symptoms were vomiting, coughing, bloody diarrhea, and stomach cramps. She tested positive for coronavirus and they also found a gastrointestinal infection (GI) and signs of colon damage. This case is one of many that suggests the virus can cause great damage to the lower digestive tract, a region rich in ACE2 receptors.

Studies have found that more than half of infected patients have viral RNA in their stool, meaning the virus is replicating in the gastrointestinal tract. Diarrhea is present in about 20% of patients, but currently, gastrointestinal symptoms aren’t included on the CDC’s list of coronavirus symptoms. The concern over RNA in feces is that it could also contain the virus. The CDC has not seen this with SARS and other related viruses, so they believe this chance is very low.

Right now, the limited research available is only able to provide theories about the effects of COVID-19 on the body. Even as researchers are working hard to understand the virus, a true picture is still years away. The number one priority right now is a vaccine and treatments to combat the virus. After this, we can begin the long journey of discovering how and why the virus is affecting the whole body and in turn, the whole world.